CN104402690B - The preparation method of method Buddhist nun's aldehyde and accompany the preparation method of auspicious tretinoin - Google Patents
The preparation method of method Buddhist nun's aldehyde and accompany the preparation method of auspicious tretinoin Download PDFInfo
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- CN104402690B CN104402690B CN201410758307.8A CN201410758307A CN104402690B CN 104402690 B CN104402690 B CN 104402690B CN 201410758307 A CN201410758307 A CN 201410758307A CN 104402690 B CN104402690 B CN 104402690B
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
- C07C45/27—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation
- C07C45/32—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen
- C07C45/37—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen of >C—O—functional groups to >C=O groups
- C07C45/38—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by oxidation with molecular oxygen of >C—O—functional groups to >C=O groups being a primary hydroxyl group
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C51/00—Preparation of carboxylic acids or their salts, halides or anhydrides
- C07C51/09—Preparation of carboxylic acids or their salts, halides or anhydrides from carboxylic acid esters or lactones
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
- C07C67/333—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton
- C07C67/343—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group by isomerisation; by change of size of the carbon skeleton by increase in the number of carbon atoms
Abstract
The invention provides the preparation method of a kind of method Buddhist nun's aldehyde, including: there is oxidation reaction in farnesol under the effect of catalyst and oxidant, obtains method Buddhist nun's aldehyde in organic solvent；Described catalyst is Cu or copper-containing compound.Present invention also offers a kind of preparation method accompanying auspicious tretinoin.The present invention is oxidized to method Buddhist nun's aldehyde with metallic copper or copper-containing compound for catalyst farnesol, not only catalytic efficiency is higher, reaction condition is gentle, and the method Buddhist nun's aldehyde purity prepared and yield are higher, it is not necessary to purification is used directly for subsequent reactions and carries out accompanying the preparation of auspicious tretinoin.It addition, the preparation method green non-pollution of method Buddhist nun's aldehyde of present invention offer, industrialized production can be realized.Test result indicate that, method Buddhist nun's aldehyde yield prepared by the method that the present invention provides is more than 85%, and purity is more than 95%.Test result indicate that, prepared by the method that the present invention provides accompanies the purity of auspicious tretinoin crude product up to more than 98%, and after recrystallizing and refining, purity is up to more than 99%.
Description
Technical field
The invention belongs to technical field of organic synthesis, particularly relate to the preparation method of a kind of method Buddhist nun's aldehyde and accompany auspicious tretinoin
Preparation method.
Background technology
Accompanying auspicious tretinoin, chemical name is (2E, 4E, 6E, 10E)-3,7,11,15-tetramethyl-2,4,6,10,14-ten six
Carbon 5 alkene acid, also known as peretinoin, English name is Peretinoin, structural formula shown in formula I:
Accompanying auspicious tretinoin is a kind of cancer treatment drugs, is currently used primarily in the treatment of hepatocarcinoma.This compound is unsaturated carboxylic
Acid compounds, its structure mainly contains carboxyl and carbon-carbon double bond Liang Zhong functional group.Therefore the construction method of double bond and carboxyl are such as
What introduces is the key issue prepared and accompany auspicious tretinoin.
At present, prior art discloses following three kinds of synthetic routes accompanying auspicious tretinoin:
Synthetic route one:
This route is with (3E, 5E, 9E)-6, and 10,14-trimethyl-3,5,9,13-ten five carbon tetraene-2-ketone are raw material, first
Be condensed with malonate, the most again through dehydration, hydrolysis, decarboxylation, purification etc. five step realize accompanying the preparation of auspicious tretinoin.
Synthetic route two:
This route is with (2E, 6E)-1-bromo-3, and 7,11-trimethyl-2,6,10-ten two carbon triolefins are initiation material, first
Reacting prepared phosphorus-containing compound with NSC 5284 through Arbuzov, this compound occurs HWE to react to accompany auspicious with corresponding aldehyde
Tretinoin ester, gained is accompanied auspicious tretinoin ester to prepare through hydrolysis and is accompanied auspicious tretinoin ester.
Synthetic route three:
This route is with (2E, 6E)--and 3,7,11-trimethyl-2,6,10-ten two carbon three olefine aldehydrs, i.e. method Buddhist nun aldehyde are for initial former
Material, reacts through HWE with 3-methyl-4-phosphono butenoic acid triethyl, and a step prepares and accompanies auspicious tretinoin ester, and gained accompanies auspicious tretinoin ester warp
Hydrolysis prepares and accompanies auspicious tretinoin.
In above-mentioned three kinds of synthetic routes, the first synthetic route step is more；Although the second synthetic route step is less,
But its raw material bromo-derivative poor stability, facile hydrolysis and toxicity are relatively big, it is difficult to operation；The third synthetic route step is few, and
Raw material is relatively stable, but, in the third synthetic route, raw material method Buddhist nun aldehyde lacks ripe synthetic method, causes accompanying of preparation auspicious
Tretinoin ester needs the method through column chromatography to separate, and is unsuitable for industrialized production.
Summary of the invention
In view of this, an object of the present invention is to provide the preparation method of a kind of method Buddhist nun's aldehyde, the side that the present invention provides
Method Buddhist nun's aldehyde prepared by method has higher purity and yield.
The two of the purpose of the present invention are to provide a kind of preparation method accompanying auspicious tretinoin, the method operation that the present invention provides
Step is simple, it is not necessary to the purification step that column chromatography etc. are complicated, preparation accompany auspicious tretinoin productivity and purity the highest.
The invention provides the preparation method of a kind of method Buddhist nun's aldehyde, including:
There is oxidation reaction in farnesol under the effect of catalyst and oxidant, obtains method Buddhist nun's aldehyde in organic solvent；
Described catalyst is Cu or copper-containing compound.
Preferably, described catalyst be Cu, copper oxide, dichloride copper or Schweinfurt green.
Preferably, described oxidant is oxygen or air；
Described organic solvent is acetonitrile, N,N-dimethylformamide or oxolane.
Preferably, the consumption of described catalyst is the 1%～10% of farnesol quality.
Preferably, the temperature of described oxidation reaction is reflux temperature, and the time of described oxidation reaction is 2h～20h.
Present invention also offers a kind of preparation method accompanying auspicious tretinoin, including:
A) there is oxidation reaction in organic solvent in farnesol under the effect of catalyst and oxidant, obtains method Buddhist nun's aldehyde；
Described catalyst is Cu or copper-containing compound；
B) described method Buddhist nun's aldehyde is after Huo Naer-Wordsworth-Ai Mengsi reaction, obtains accompanying auspicious tretinoin ester；
C) accompany auspicious tretinoin ester described in after hydrolysis, obtain accompanying auspicious tretinoin.
Preferably, in described step a), described catalyst is Cu, copper oxide, dichloride copper or Schweinfurt green；
Described oxidant is oxygen or air；
Described organic solvent is acetonitrile, N,N-dimethylformamide or oxolane；
The consumption of described catalyst is 1wt%～10wt% of farnesol quality；
The temperature of described oxidation reaction is reflux temperature, and the time of described oxidation reaction is 2h～20h.
Preferably, the product that step a) obtains is directly used in step b) without refined；
The product that step b) obtains is directly used in step c) without refined.
Preferably, step c) including:
C1) accompany auspicious tretinoin ester described in after hydrolysis, obtain accompanying auspicious tretinoin crude product；
C2) accompany auspicious tretinoin crude product through recrystallization described in, obtain accompanying auspicious tretinoin.
Preferably, described step c2) in, recrystallization solvent is methanol, ethanol or the mixed solvent of second alcohol and water.
The preparation method of a kind of method Buddhist nun's aldehyde that the present invention provides, comprises the following steps: farnesol is at catalyst and oxidant
Effect under there is oxidation reaction in organic solvent, obtain method Buddhist nun's aldehyde；Described catalyst is Cu or copper-containing compound.The present invention
Being oxidized to method Buddhist nun's aldehyde with metallic copper or copper-containing compound for catalyst farnesol, not only catalytic efficiency is higher, reaction condition
Gentleness, and the method Buddhist nun's aldehyde purity prepared and yield are higher, it is not necessary to and purification is used directly for subsequent reactions to carry out accompanying auspicious tretinoin
Preparation.It addition, the preparation method green non-pollution of method Buddhist nun's aldehyde of present invention offer, industrialized production can be realized.Experimental result
Showing, method Buddhist nun's aldehyde yield prepared by the method that the present invention provides is more than 85%, and purity is more than 95%.
Further, after the present invention prepares high-purity method Buddhist nun's aldehyde, Huo Naer-Wordsworth-Ai Meng is passed it through
This reacts (HWE reaction), obtains high-purity and accompanies auspicious tretinoin ester；This accompanies auspicious tretinoin ester to need not move through the complicated purification such as column chromatography
Process can directly be hydrolyzed reaction preparation purity higher accompany auspicious tretinoin.Test result indicate that, the method that the present invention provides
That prepares accompanies the purity of auspicious tretinoin crude product up to more than 98%, and after recrystallizing and refining, purity is up to more than 99%.
Accompanying drawing explanation
Fig. 1 is the hydrogen nuclear magnetic resonance spectrogram of the product that the embodiment of the present invention 1 prepares；
Fig. 2 is the HPLC collection of illustrative plates of the product that the embodiment of the present invention 1 prepares；
Fig. 3 is the hydrogen nuclear magnetic resonance spectrogram of the product that the embodiment of the present invention 4 prepares；
Fig. 4 is the carbon-13 nmr spectra figure of the product that the embodiment of the present invention 4 prepares；
Fig. 5 is the HPLC spectrogram of the product that the embodiment of the present invention 4 prepares.
Detailed description of the invention
The invention provides the preparation method of a kind of method Buddhist nun's aldehyde, including:
There is oxidation reaction in farnesol under the effect of catalyst and oxidant, obtains method Buddhist nun's aldehyde in organic solvent；
Described catalyst is Cu or copper-containing compound.
The present invention, with farnesol as raw material, carries out the preparation of method Buddhist nun's aldehyde for catalyst, no with metallic copper or copper-containing compound
Only catalytic efficiency is higher, reaction condition is gentle, and the method Buddhist nun's aldehyde purity prepared and yield are higher, it is not necessary to purification can directly be used
Carry out accompanying the preparation of auspicious tretinoin in subsequent reactions.
Farnesol, Chinese is 3,7,11-trimethyl-2,6,10-dodecane triolefin-1-alcohol, structural formula such as Formula II institute
Show:
The source of described farnesol is not particularly limited by the present invention, the product that market is bought.
The present invention aoxidizes using metallic copper or copper-containing compound as catalyst farnesol, and described copper-containing compound includes
But it is not limited to copper oxide, dichloride copper, Schweinfurt green etc.；Described catalyst is preferably metallic copper or copper oxide.In the present invention, institute
The consumption stating catalyst is preferably the 1%～10% of farnesol quality, more preferably 2%～8%.
In the present invention, described oxidant is preferably oxygen or air.
The present invention is using organic solvent as reaction medium, and described organic solvent includes but not limited to acetonitrile, N, N-dimethyl
Methanamide or oxolane, preferably acetonitrile.
Farnesol and catalyst are joined in organic solvent by the present invention, carry out oxidation reaction, make method after being passed through oxidant
Buddhist nun's alcohol is oxidized to method Buddhist nun's aldehyde, i.e. (2E, 6E)--3,7,11-trimethyl-2,6,10-ten two carbon three olefine aldehydrs.In the present invention, described
The temperature of oxidation reaction is preferably reflux temperature, and the time of described oxidation reaction is preferably 2h～20h, more preferably 4h～15h.
After completion of the reaction, the product that obtains is filtered, carry out the filter cake obtained washing, compress after i.e. can get method
Buddhist nun's aldehyde.As preferably, the present invention uses acetonitrile to wash filter cake, after obtaining organic facies, by its concentrating under reduced pressure, the most available
Method Buddhist nun's aldehyde.The present invention, without refining the method Buddhist nun's aldehyde obtained further, i.e. can be used for next step preparation and accompanies auspicious tretinoin.
After obtaining method Buddhist nun's aldehyde, it being carried out nuclear magnetic resonance spectroscopy and HPLC analyzes, result shows, it has the knot of method Buddhist nun's aldehyde
Structure.
Present invention also offers a kind of preparation method accompanying auspicious tretinoin, including:
A) there is oxidation reaction in organic solvent in farnesol under the effect of catalyst and oxidant, obtains method Buddhist nun's aldehyde；
Described catalyst is Cu or copper-containing compound；
B) described method Buddhist nun's aldehyde is after Huo Naer-Wordsworth-Ai Mengsi reaction, obtains accompanying auspicious tretinoin ester；
C) accompany auspicious tretinoin ester described in after hydrolysis, obtain accompanying auspicious tretinoin.
Being first according to method as described above and prepare method Buddhist nun's aldehyde, the present invention does not repeats them here.
After obtaining method Buddhist nun's aldehyde, it is not necessary to method Buddhist nun's aldehyde is carried out the refined preparation that i.e. can be used for accompanying auspicious tretinoin ester.In the present invention
In, described method Buddhist nun's aldehyde, after Huo Naer-Wordsworth-Ai Mengsi reaction (HWE reaction), i.e. can obtain accompanying auspicious tretinoin ester.
Specifically, there is HWE reaction in method Buddhist nun's aldehyde, 3-methyl-4-phosphono butenoic acid triethyl and sodium hydroxide, is accompanied
Auspicious tretinoin ester, i.e. (2E, 4E, 6E, 10E)-3,7,11,15-tetramethyl-2,4,6,10,14-ten six carbon 5 alkene acid ethyl esters, one
Individual typical preparation process is as follows:
3-methyl-4-phosphono butenoic acid triethyl is dissolved in toluene, after dropping sodium hydroxide reaction, adds method Buddhist nun's aldehyde
React, i.e. can obtain accompanying auspicious tretinoin ester.
After completion of the reaction, by the reactant liquor separatory obtained, wash, be dried, i.e. can obtain accompanying auspicious tretinoin after concentrating under reduced pressure
Ester, it is not necessary to refine and be directly used in subsequent reactions.
Accompany auspicious tretinoin ester after hydrolysis, i.e. can obtain accompanying auspicious tretinoin, i.e. (2E, 4E, 6E, 10E)-3,7,11,15-tetramethyls
Base-2,4,6,10,14-ten six carbon 5 alkene acids, the typical hydrolytic process of one is as follows:
Add after potassium hydroxide is dissolved in isopropanol and accompany auspicious tretinoin ester, after back flow reaction, the reactant liquor obtained is divided
Liquid, washs, is dried, obtains accompanying auspicious tretinoin crude product after concentrating under reduced pressure.
After obtaining accompanying auspicious tretinoin crude product, being carried out recrystallization, i.e. can get high purity 99% accompanies auspicious tretinoin.?
In the present invention, the solvent used by recrystallization is preferably methanol, ethanol or the mixed solvent of second alcohol and water.
The present invention, with farnesol as raw material, carries out HWE anti-after metallic copper or copper-containing compound are catalytically oxidized to method Buddhist nun's aldehyde
Should, then obtain accompanying auspicious tretinoin after hydrolysis, its course of reaction is as follows:
After obtaining accompanying auspicious tretinoin, it being carried out nuclear magnetic resonance spectroscopy and HPLC analyzes, result shows, it has accompanies auspicious dimension A
The structure of acid.
After the present invention prepares high-purity method Buddhist nun's aldehyde, pass it through Huo Naer-Wordsworth-Ai Mengsi and react (HWE
Reaction), obtain high-purity and accompany auspicious tretinoin ester；This accompanies auspicious tretinoin ester to need not move through the complicated purge processes such as column chromatography can be straight
Tap into row hydrolysis prepare purity higher accompany auspicious tretinoin.Test result indicate that, prepared by the method that the present invention provides accompanying is auspicious
The purity of tretinoin crude product is up to more than 98%, and after recrystallizing and refining, purity is up to more than 99%.
The preparation method of the method Buddhist nun's aldehyde present invention provided below in conjunction with embodiment and accompany the preparation method of auspicious tretinoin to carry out
Describe in detail.
Embodiment 1
Farnesol (72.27g, 0.32mol) is placed in 500mL round-bottomed flask, in system add 280.0mL acetonitrile and
Metallic copper (2.08g, 32.5mmol), is passed through oxygen, and heating systems, to backflow, maintains backflow 4 hours, the product that will obtain
Filter, filter cake with 100mL acetonitrile wash, merge organic to, concentrating under reduced pressure obtains pale yellow oil 68.32g.
Described pale yellow oil is carried out hydrogen nuclear magnetic resonance analysis of spectrum, and it is the embodiment of the present invention 1 that result sees Fig. 1, Fig. 1
The hydrogen nuclear magnetic resonance spectrogram of the product prepared.
Described pale yellow oil is carried out HPLC analysis, and result sees Fig. 2 and Biao 1, and Fig. 2 is that the embodiment of the present invention 1 is made
The HPLC collection of illustrative plates of the standby product obtained, table 1 is the HPLC spectral data of the product of the embodiment of the present invention 1 preparation.
The HPLC peak data of the product of table 1 embodiment of the present invention 1 preparation
From Fig. 1, Fig. 2 and Biao 1, the present invention has prepared method Buddhist nun's aldehyde, and its productivity is 95%, and purity is 97.0%.
Embodiment 2
Farnesol (72.27g, 0.32mol) is placed in 500mL round-bottomed flask, in system add 280.0mL acetonitrile and
Copper oxide (5.20g, 65.0mmol), is passed through oxygen, and heating systems, to backflow, maintains backflow 7 hours, the product that will obtain
Filter, filter cake with 100mL acetonitrile wash, merge organic to, concentrating under reduced pressure obtains pale yellow oil 62.32g.
Described pale yellow oil carrying out hydrogen nuclear magnetic resonance analysis of spectrum and HPLC analyzes, result shows, the present invention obtains
Method Buddhist nun's aldehyde, its productivity is 86%, purity is 96.8%.
Embodiment 3
Farnesol (72.27g, 0.32mol) is placed in 500mL round-bottomed flask, in system, adds 280.0mL tetrahydrochysene furan
Mutter and metallic copper (2.08g, 32.5mmol), be passed through oxygen, heating systems to 80 DEG C, it is stirred at reflux 12 hours, anti-by obtain
Answer product to filter, filter cake with 100mL oxolane wash, merge organic to, concentrating under reduced pressure obtains pale yellow oil 64.31g.
Described pale yellow oil carrying out hydrogen nuclear magnetic resonance analysis of spectrum and HPLC analyzes, result shows, the present invention obtains
Method Buddhist nun's aldehyde, its productivity is 91%, purity is 95.7%.
Embodiment 4
3-methyl-4-phosphono butenoic acid triethyl (78.72g, 0.30) is added with thermometer and reflux condensing tube
In there-necked flask, adding 300mL toluene in system, system is cooled to-10 DEG C, the sodium hydroxide solution of dropping 50%
(200mL) reaction 2h, then it is warmed to room temperature.System is down to-10 DEG C in system, drips method Buddhist nun's aldehyde prepared by embodiment 1
(50.00g) toluene (50mL) solution.1h is stirred at room temperature.The reactant liquor separatory that will obtain, organic facies is respectively with saturated ammonium chloride
Washing with saturated aqueous common salt (200mL) of solution (200mL × 2), is then dried with anhydrous sodium sulfate, and concentrating under reduced pressure obtains faint yellow
Grease accompanies auspicious tretinoin ester 74.29g, it is not necessary to refines and is directly used in subsequent reactions.
Potassium hydroxide (30.00g) is added in the there-necked flask with thermometer and reflux condensing tube, add in system
300mL isopropanol, nitrogen protects, and system is warming up to 100 DEG C, treats potassium hydroxide to be completely dissolved in backward system to add above-mentioned yellowish
Color grease accompanies auspicious tretinoin ester (74.00g), maintenance system backflow 1h.300mL cold water and the normal hexane of 300mL in system.
The reactant liquor separatory that will obtain, aqueous phase is with 10% dilute hydrochloric acid regulation pH value to 6～7, and normal hexane (300mL × 2) extracts；Organic facies
Washing with saturated ammonium chloride solution (200mL × 2) and saturated aqueous common salt (200mL) respectively, organic facies is dried with anhydrous sodium sulfate,
Concentrating under reduced pressure obtains pale yellow oil and accompanies auspicious tretinoin crude product 68.32g, and purity is 98.5%.
Pale yellow oil is accompanied auspicious tretinoin crude product 68.00g add with thermometer and the there-necked flask of reflux condensing tube
In, in system, add 680mL methanol, be warming up to reflux (55～60 DEG C), stir 20min.Auspicious tretinoin crude product is accompanied to be completely dissolved
After by system lucifuge in-20 DEG C of stirring and crystallizing 24h.Filter, the lower 45 DEG C of vacuum drying of solid lucifuge, obtain yellow or pale yellow crystals
Property powder 34.28g.
Described crystalline powder is carried out nuclear magnetic resoance spectrum map analysis, and it is that the present invention implements that result sees Fig. 3 and Fig. 4, Fig. 3
The hydrogen nuclear magnetic resonance spectrogram of the product that example 4 prepares, Fig. 4 is the nuclear magnetic resonance, NMR of the product that the embodiment of the present invention 4 prepares
Carbon spectrogram.
Described crystalline powder is carried out HPLC analysis, and result sees Fig. 5 and Biao 2, and Fig. 5 is prepared by the embodiment of the present invention 4
The HPLC spectrogram of the product obtained, table 2 is the HPLC spectral data of the product that the embodiment of the present invention 4 prepares.
The HPLC spectral data of the product that table 2 embodiment of the present invention 4 prepares
From Fig. 3, Fig. 4, Fig. 5 and Biao 2, the present invention has prepared and has accompanied auspicious tretinoin, and its gross production rate is 35%, purity
It is 99.82%.
The above is only the preferred embodiment of the present invention, it is noted that for the ordinary skill people of the art
For Yuan, under the premise without departing from the principles of the invention, it is also possible to make some improvements and modifications, these improvements and modifications also should
It is considered as protection scope of the present invention.
Claims (7)
1. a preparation method for method Buddhist nun aldehyde, including:
There is oxidation reaction in farnesol under the effect of catalyst and oxidant, obtains method Buddhist nun's aldehyde in organic solvent；
Described catalyst is copper oxide, dichloride copper or Schweinfurt green；
Described oxidant is oxygen；
Described organic solvent is acetonitrile；
The temperature of described oxidation reaction is reflux temperature, and the time of described oxidation reaction is 2h～20h.
Preparation method the most according to claim 1, it is characterised in that the consumption of described catalyst is farnesol quality
1%～10%.
3. accompany a preparation method for auspicious tretinoin, including:
A) there is oxidation reaction in organic solvent in farnesol under the effect of catalyst and oxidant, obtains method Buddhist nun's aldehyde；Described
Catalyst is copper oxide, dichloride copper or Schweinfurt green；Described oxidant is oxygen；Described organic solvent is acetonitrile；
The temperature of described oxidation reaction is reflux temperature, and the time of described oxidation reaction is 2h～20h；
B) described method Buddhist nun's aldehyde is after Huo Naer-Wordsworth-Ai Mengsi reaction, obtains accompanying auspicious tretinoin ester；
C) accompany auspicious tretinoin ester described in after hydrolysis, obtain accompanying auspicious tretinoin.
Preparation method the most according to claim 3, it is characterised in that in described step a),
The consumption of described catalyst is 1wt%～10wt% of farnesol quality.
Preparation method the most according to claim 3, it is characterised in that the product that step a) obtains is without refined direct
For step b)；
The product that step b) obtains is directly used in step c) without refined.
Preparation method the most according to claim 3, it is characterised in that step c) including:
C1) accompany auspicious tretinoin ester described in after hydrolysis, obtain accompanying auspicious tretinoin crude product；
C2) accompany auspicious tretinoin crude product through recrystallization described in, obtain accompanying auspicious tretinoin.
Preparation method the most according to claim 6, it is characterised in that described step c2) in, recrystallization solvent be methanol,
Ethanol or the mixed solvent of second alcohol and water.
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| CN104177241B (en) * | 2014-06-23 | 2017-01-11 | 华东师范大学 | Alkynyl diketone compound and synthetic method thereof |
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| CN1706548A (en) * | 2004-06-07 | 2005-12-14 | 花王株式会社 | Process for producing aldehyde |
| CN103626649A (en) * | 2013-11-07 | 2014-03-12 | 深圳万乐药业有限公司 | Method of preparing pelretin A acid |
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